The invention relates to compounds as defined hereinafter, which constitute a class of medicaments having mainly an anti-inflammatory activity and/or acting by inhibiting LTA4 (leukotriene A4) hydrolase, an enzyme which is responsible for the biosynthesis of leukotriene LTB4, a major proinflammatory mediator.
It also relates to such compounds useful for forming prodrugs.
It also relates to methods for preparing these compounds.
LTA4 hydrolase (EC 3.3.2.6.) is an enzyme which is in particular present in the neutrophils and whose sequence has been recently shown (Funck et al., P.N.A.S., 1987, 89: 6677) to be related to that of a zinc metallopeptidase, aminopeptidase M (Malfroy et al., B.B.R.C., 1989, 161: 236). In agreement with the suggestion by Malfroy et al., it has been recognized that LTA4 possesses a zinc atom which is essential for its catalytic activity, an aminopeptidase-type activity, and is sensitive to the action of certain metallopeptidase inhibitors (Heggstrom et al., B.B.R.C., 1990, 173: 431; Minami et al., B.B.R.C., 1990, 173: 620).
The inhibition of LTA4 hydrolase is capable of preventing formation of LTB4, a mediator responsible for the adhesion of the neutrophils to the endothelial cells and for their chemotaxis. It appears to be involved in the aetiology or the symptomatology of a variety of conditions and inflammatory states such as rheumatoid arthritis, chronic inflammations of the intestine, multiple sclerosis, gout and psoriasis. In these processes, LTB4 is thought to act in synergy with other metabolites of arachidonic acid which are produced by 5-lipoxygenase or cyclooxygenases whose inhibition is well known to produce anti-inflammatory effects.
Some LTA4 hydrolase inhibiting compounds have been described, in particular in patent applications WO 94/00420, WO 96/11192, WO 96/10999 and WO 96/27585.
The objective of the present invention is to provide novel compounds capable of inhibiting LTA4 hydrolase.
The objective of the present invention is also to provide compounds which can be used as medicaments.
To this end, the subject of the invention is compounds of formula (I) as defined below.
Its subject is also pharmaceutical compositions containing at least one such compound.
Its subject is also the use of compounds of formula (I) as defined below, as medicaments which act as inhibitor of the activity of LTA4 hydrolase, in particular as anti-inflammatory agents.
The subject of the invention is also the use of compounds of formula (I) in the form of prodrugs.
The inventors have demonstrated that the compounds of formula (I), or their salts obtained with therapeutically acceptable inorganic or organic acids or their stereoisomers, possessed an LTA4 hydrolase inhibiting activity.
The compounds (I) according to the invention have, moreover, good bioavailability.
The present invention describes a series of compounds capable of potently inhibiting LTA4 hydrolase.
These compounds have, in addition, a biological activity as indicated below, which makes them therapeutically useful.
The compounds according to the invention correspond to the following formula (I): 
in which:
X is chosen from the following groups:
i) xe2x80x94NH2 
R1 and R2 are independently chosen from the following groups:
i) a hydrogen atom
ii) a lower alkyl group
iii a lower alkyl group substituted with a halogen atom
iv) CF3 
v) a halogen atom;
n1 varies from 1 to 4
n2 varies from 0 to 10
R3 is chosen from the following groups:
i) a hydrogen atom 
Y is chosen from the following groups:
i) xe2x80x94Oxe2x80x94
ii) xe2x80x94CH2xe2x80x94
iii ) xe2x80x94Sxe2x80x94
iv) xe2x80x94OCH2xe2x80x94
v) xe2x80x94SCH2xe2x80x94
vi) xe2x80x94NHxe2x80x94
Ar is chosen from the following groups:
i) a phenyl group which is unsubstituted or which is mono- or polysubstituted with substituents chosen from halogen atoms and CF3, lower alkyl, lower alkoxy, NH2, NO2, CN, OH, CO2H, OPh, OCH2Ph, SMe, SEt, Ph, CH2Ph and NHCOR7 groups where R7 is a lower alkyl group, 
R4 and R5 are independently chosen from the following groups: an unsubstituted phenyl group, a phenyl group which is mono- or polysubstituted with substituents chosen from halogen atoms and CF3, NO2, CN, OH, lower alkyl and lower alkoxy groups;
R6 represents a lower alkyl group or a phenyl group.
The expression lower alkyl group is understood to mean an alkyl group having a linear or branched chain containing form 1 to 6 carbon atoms, such as methyl, ethyl, propyl, butyl, pentyl, hexyl and their branched isomers.
The expression lower alkoxy group is understood to mean an alkoxy group containing a linear or branched chain having 1 to 6 carbon atoms, such as methoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy and their branched isomers.
The halogen atoms are preferably chosen from chlorine and fluorine.
When a bond is drawn through a bond in a ring, this indicates that the bond may be linked to any available atom in this ring.
The invention also comprises the isomers of the compounds of formula (I), including the diastereoisomeric and enantiomeric forms.
The invention also extends to the therapeutically acceptable salts of these compounds, as well as to the salts of their isomers, including the diastereoisomeric and enantiomeric forms.
The expression therapeutically acceptable salts is understood to mean a salt which does not adversely affect either the chemical structure or the pharmacological properties of the compounds of the present invention. Such salts include inorganic or organic anions such as hydrochloride, hydrobromide, acetate, trifluoroacetate, maleate, fumarate, oxalate and the like, which are well known in the art. These salts are prepared in a conventional manner by neutralizing the compounds of formula (I) with the desired acid.
Among the compounds of formula (I) which is cited above, those for which X represents NH2 and/or R3 represents a hydrogen atom are preferred.
In this group, the compounds of formula (I) in which X is NH2 and R3 is a hydrogen atom are more particularly preferred.
The compounds of formula (I) for which R1 represents a hydrogen atom also constitute a particularly preferred subgroup according to the invention.
The compounds of formula (I) with R1 different from hydrogen represent another subgroup according to the invention.
A subfamily among the abovementioned compounds is formed by the compounds for which n1 is equal to 1.
Another subfamily consists of the compounds for which n1 is different from 1.
In accordance with the invention, R2 preferably represents a hydrogen atom.
Another subgroup of compounds according to the invention is formed by the compounds where R2 is different from a hydrogen atom. In this case, R2 preferably represents a methyl group.
A subclass of compounds according to the invention also consists of those for which n2 is equal to zero. Among these compounds, Y preferably represents xe2x80x94Oxe2x80x94, xe2x80x94Sxe2x80x94, xe2x80x94OCH2xe2x80x94, xe2x80x94SCH2xe2x80x94 or xe2x80x94NHxe2x80x94.
Another subclass is formed by the compounds for which n2 varies from 1 to 4, preferably from 2 to 4, and in a more particularly preferred manner by the compounds where n2 is equal to 3.
Another class of compounds according to the invention is defined by those where n2 is greater than 4.
From the point of view of the symbol Y, the compounds for which the latter represents an oxygen atom are particularly preferred according to the invention.
Other subfamilies may be defined according to whether Y represents xe2x80x94CH2xe2x80x94, a sulphur atom, a group xe2x80x94CH2xe2x80x94 or xe2x80x94SCH2xe2x80x94 or alternatively a unit xe2x80x94NHxe2x80x94.
Ar is preferably chosen from a phenyl group which is unsubstituted or substituted, more preferably monosubstituted, with one of the abovementioned substituents.
When Ar symbolizes a substituted phenyl group, the substituent(s) are preferably chosen from halogen atoms, CF3, lower alkyl, O(lower alkyl), NO2, CN, CO2H, OPh, OCH2Ph, Ph and CH2Ph groups, the halogen atoms as well as the lower alkyl and O(lower alkyl) groups being more particularly preferred.
The compounds for which Ar is a phenyl group which is mono- or polysubstituted with xe2x80x94OPh, xe2x80x94OCH2Ph, xe2x80x94Ph or xe2x80x94CH2Ph constitute another subfamily according to the invention.
Other subclasses are also defined according to whether Ar represents a naphthyl, pyridinyl or benzodioxazole group.
For all the abovementioned subfamilies, the substituents not specified may vary according to their respective general definitions.
A particularly preferred group of compounds according to the invention consists of the compounds corresponding to the following formula (II): 
in which X, R2, R3, Y, Ar and n2 have the above meanings.
The preferences indicated above for the compounds of formula (I) also apply to those of formula (II).
A group which is even more particularly preferred comprises the compounds corresponding to the following formula (III): 
in which Y, Ar and n2 have the meaning indicated above.
The particular choices mentioned for the compounds of formula (I) from the point of view of the symbols Y and Ar also apply to the compounds of formula (III).
Among the compounds of formula (II) or (III), those for which n2 is equal to 3, Y represents an oxygen atom and Ar represents a phenyl group which is unsubstituted or substituted as indicated above, where appropriate R2 representing a methyl group and R3 representing the unit iv) mentioned above, are particularly preferred according to the invention.
Examples of compounds of the present invention are:
(S)-2-amino-3-phenoxy-1-propanethiol hydrochloride
(S)-2-amino-3-benzyloxy-1-propanethiol hydrochloride
(R)-2-amino-3-benzyloxy-1-propanethiol hydrochloride
(2S,3R)-2-amino-3-methyl-3-benzyloxy-1-propanethiol hydrochloride
(2R,3S)-2-amino-3-methyl-3-benzyloxy-1-propanethiol hydrochloride
(S)-2-amino-3-benzylthio-1-propanethiol hydrochloride
(R,S)-2-amino-7-phenyl-1-heptanethiol hydrochloride
(R,S)-2-amino-2-methyl-6-phenoxy-1-hexanethiol hydrochloride
(S)-2-amino-3-(4-benzylphenoxy)-1-propanethiol hydrochloride
(R,S)-2-amino-4-phenyl-1-butanethiol hydrochloride
(R,S) -2-amino-6-phenoxy-1-hexanethiol hydrochloride
(R,S)-2-amino-7-phenoxy-1-heptanethiol hydrochloride
(R,S)-2-amino-7-(4-methoxyphenoxy)-1-heptanethiol hydrochloride
(R,S)-2-amino-6-(4-methoxyphenoxy)-1-hexanethiol hydrochloride
(R,S)-2-amino-6-(4-methylphenoxy)-1-hexanethiol hydrochloride
(R,S)-2-amino-6-(3-methylphenoxy)-1-hexanethiol hydrochloride
(R,S)-2-amino-6-(3-methoxyphenoxy)-1-hexanethiol hydrochloride
(R,S)-2-amino-6-(4-chlorophenoxy)-1-hexanethiol hydrochloride
(R,S)-2-amino-6-(4-bromophenoxy)-1-hexanethiol hydrochloride
(R,S)-2-amino-6-(4-fluorophenoxy)-1-hexanethiol hydrochloride
(R,S)-2-amino-6-(2-methoxyphenoxy)-1-hexanethiol hydrochloride
(R,S)-2-amino-6-phenylthio-1-hexanethiol hydrochloride
(R,S)-2-amino-6-(3,4-dioxymethylenephenoxy)-1-hexanethiol hydrochloride
(R,S)-2-amino-6-(4-ethoxyphenoxy)-1-hexanethiol hydrochloride
(R,S)-2-amino-6-(4-ethylphenoxy)-1-hexanethiol hydrochloride
(R,S)-2-amino-5-phenyl-1-pentanethiol hydrochloride
(R,S)-2-amino-4-phenoxy-1-butanethiol hydrochloride
(R,S)-2-amino-6-phenyl-1-hexanethiol hydrochloride
(R,S)-2-amino-4-phenylthio-1-butanethiol hydrochloride
(R,S)-2-amino-6-(2,6-dimethylphenoxy)-1-hexanethiol hydrochloride
(R,S)-2-amino-4-benzylthio-1-butanethiol hydrochloride
(R,S)-2-amino-5-phenoxy-1-pentanethiol hydrochloride
(R,S)-2-amino-6-(2-methylphenoxy)-1-hexanethiol hydrochloride
(R,S)-2-amino-6-(4-phenoxyphenoxy)-1-hexanethiol hydrochloride
(R,S)-2-amino-6-(4-carboxyphenoxy)-1-hexanethiol hydrochloride
(R,S)-2-amino-6-(4-cyanophenoxy)-1-hexanethiol hydrochloride
[2(R,S)-3(R,S)]-2-amino-3-methyl-6-phenoxy-1-hexanethiol hydrochloride
(R S)-2-amino-6-(4-phenylphenoxy)-1-hexanethiol hydrochloride
(R,S)-2-amino-6-(4-benzyloxyphenoxy)-1-hexanethiol hydrochloride
(R,S)-2-amino-6-(2-naphthyloxy)-1-hexanethiol hydrochloride
(R,S)-2-amino-6-(1-naphthyloxy)-1-hexanethiol hydrochloride
(R,S)-2-amino-8-phenoxy-1-octanethiol hydrochloride
(R,S)-2-amino-9-phenoxy-1-nonanethiol hydrochloride
(R,S)-2-amino-6-(3-trifluoromethylphenoxy)-1-hexanethiol hydrochloride
(R,S)-2-amino-6-(3-fluorophenoxy)-1-hexanethiol hydrochloride
(R,S)-2-amino-6-(2,4-difluorophenoxy)-1-hexanethiol hydrochloride
(R,S)-2-amino-6-(2-fluorophenoxy)-1-hexanethiol hydrochloride
(R,S)-2-amino-6-pentafluorophenoxy-1-hexanethiol hydrochloride
(R,S)-2-amino-6-(4-nitrophenoxy)-1-hexanethiol hydrochloride
(R,S)-2-amino-8-phenyl-1-octanethiol hydrochloride
(R,S)-2-amino-6-(3,5-dimethoxyphenoxy)-1-hexanethiol hydrochloride
(R,S)-2-amino-6-(4-butoxyphenoxy)-1-hexanethiol hydrochloride
(R,S)-2-amino-6-(4,5-dichlorophenoxy)-1-hexanethiol hydrochloride
(R,S)-2-amino-6-(2-pyridoxy)-1-hexanethiol hydrochloride
(R,S)-2-amino-6-(3-cyanophenoxy)-1-hexanethiol hydrochloride
(R,S)-2-amino-5-(4-benzylphenoxy)-1-pentanethiol hydrochloride
(R,S)-2-amino-6-(3-chlorophenoxy)-1-hexanethiol hydrochloride
(R,S)-2-amino-7-(4-cyanophenoxy)-1-heptanethiol hydrochloride
(R,S)-2-amino-5-(4-cyanophenoxy)-1-pentanethiol hydrochloride
(R,S)-2-amino-6-(3-ethylphenoxy)-1-hexanethiol hydrochloride
(R,S)-2-amino-6-(4-trifluoromethylphenoxy)-1-hexanethiol hydrochloride
(R,S)-2-amino-7-(4-benzylphenoxy)-1-heptanethiol hydrochloride
(R,S)-2-amino-6-(4-benzylphenoxy)-1-hexanethiol hydrochloride
(R,S)-2-amino-5-(3-ethylphenoxy)-1-pentanethiol hydrochloride
(R,S)-2-amino-5-(4-methylphenoxy)-1-pentanethiol hydrochloride
(R,S)-2-amino-6-(4-acetamidophenoxy)-1-hexanethiol hydrochloride
(R,S)-2-amino-6-(4-iodophenoxy)-1-hexanethiol hydrochloride
(R,S)-2-amino-6-(4-propoxyphenoxy)-1-hexanethiol hydrochloride
(R,S)-2-amino-5-(4-benzoylphenoxy)-1-pentanethiol hydrochloride
(R,S)-2-amino-5-(4-ethoxyphenoxy)-1-pentanethiol hydrochloride
(R,S)-2-amino-7-(4-ethoxyphenoxy)-1-heptanethiol hydrochloride
(+)-2-amino-6-(4-ethoxyphenoxy)-1-hexanethiol hydrochloride
(xe2x88x92)-2-amino-6-(4-ethoxyphenoxy)-1-hexanethiol hydrochloride
(+)-2-amino-6-phenoxy-1-hexanethiol hydrochloride
(xe2x88x92)-2-amino-6-phenoxy-1-hexanethiol hydrochloride.
The compounds of formula (I) or (II) as defined above with 
and/or R3 different from the hydrogen atom, that is to say chosen from the groups 
constitute prodrugs.
Among these compounds, those of the disulphide type, in particular with R3 representing the group iv) above, are preferred prodrugs.
Examples of prodrugs according to the invention are:
1,1-dithiobis(2-(R,S)-amino-6-phenoxyhexane) dihydrochloride
(R,S)-2-amino-6-phenoxy-1-S-acetylthiohexane hydrobromide
1,1-dithiobis(2-(+)-amino-6-phenoxyhexane) dihydrochloride (A isomer)
1,1-dithiobis(2-(xe2x88x92)-amino-6-phenoxyhexane) dihydrochloride (B isomer)
1,1-dithiobis(2-(R,S)-amino-6-(4-ethoxyphenoxy)-1-hexane) dihydrochloride
1,1-dithiobis(2-(+)-amino-6-(4-ethoxyphenoxy)-1-hexane) dihydrochloride (A isomer)
1,1-dithiobis(2-(xe2x88x92)-amino-6-(4-ethoxyphenoxy)-1-hexane) dihydrochloride (B isomer)
1,1-dithiobis(2-(R,S)-amino-6-(4-acetamidophenoxy)-1-hexane dihydrochloride
1,1-dithiobis(2-(R,S)-amino-6-(4-cyanophenoxy)-1-hexane dihydrochloride.
The compounds of the present invention are prepared from easily available raw materials according to one of the methods indicated below.
The reaction schemes given below describe methods which may be used for the preparation of the compounds of formula (I), indicating the starting materials, the intermediates as well as the synthesis conditions.
The abbreviations used in the present description correspond to the definitions below:
Ac: acetyl
Bn: benzyl
DCC: dicyclohexylcarbodiimide
DEAD: diethyl azodicarboxylate
DIAD: diisopropyl azodicarboxylate
DMF: dimethylformamide
DPPA: diphenylphosphoryl azide
Et: ethyl
EtOH: ethyl alcohol
Et2O: ethyl ether
HOBT: hydroxybenzotriazole
LAH: lithium aluminium hydride
Me: methyl
Ms: methanesulphonyl
n.Bu: n-butyl
NBu4F: butylammonium fluoride
NEt3 : triethylamine
n.Pr: n-propyl
Pd/C: palladium on carbon
Ph: phenyl
tBu: tert-butyl
TFA: trifluoroacetic acid
THF :tetrahydrofuran
Ts: para-toluenesulphonyl
Schemes 1 to 3 describe the preparation of substituted amino alcohols. 
Scheme 1 describes a method for preparing the compounds of formula 3 from commercial amino acids.
Compounds 2 are easily obtained by esterification, in the presence of thionyl chloride and EtOH, of the amino acid 1. The amino alcohol 3 is obtained in 2 steps after releasing the amine with NEt3 and then reducing with LAH in Et2O at room temperature. 
R1, n2, Y and Ar are as defined in formula (I).
a) KOH, EtOH, 0xc2x0 C.
b) DPPA, NEt3, toluene, benzyl alcohol, 80xc2x0 C.
c) H2, Pd/C, EtOH
d) HCl 3N
f) NEt3, Et2O, CHCl3 
g) LAH, Et2O
The malonates of formula 4 are obtained by alkylating a malonate with the corresponding brominated or chlorinated derivatives in the presence of sodium ethoxide in ethanol under reflux. Monosaponification using a solution of KOH in EtOH gives the compounds 5 which are subjected to a Curtius reaction in the presence of DPPA, NEt3 and benzyl alcohol in toluene at 80xc2x0 C. overnight.
The benzyloxycarbonyl functional group is deprotected by catalytic hydrogenation in ethanol using Pd/C to give the amino esters 7. The amino alcohols 8 are obtained as described in scheme 1. 
The serine or the threonine is esterified in the presence of thionyl chloride and EtOH. The amino ester hydrochloride 9 obtained is treated with triethylamine and then with trimethylsilyl chloride in the presence of NEt3 to give the compound 10. The amino functional group is deprotected using anhydrous MeOH and then reprotected by reacting with trityl chloride. The hydroxyl functional group is then released using tetrabutylammonium fluoride to give the compound 11. The hydroxyl functional group of compound 11 is substituted by a Mitsunobu-type reaction with a phenolic derivative of formula 
to give the compound 12. The compounds 14 are obtained by deprotection with formic acid followed by reduction using lithium aluminium hydride.
Scheme 4 describes a method for preparing compounds 17 corresponding to formula (I). 
The amino functional group of compounds 3, 8 or 14 is protected using trifluoroacetylimidazole in pyridine at 0xc2x0 C. A Mitsunobu-type reaction is then carried out on compounds 15 in the presence of PPh3, DEAD (or DIAD) and thioacetic acid to give compounds 16. Finally, compounds 17 are obtained by deprotection at 50xc2x0 C. in a basic medium under an inert atmosphere followed by acidification with an aqueous hydrochloric acid solution.
For the synthesis of compounds 30 of formula (I), a method via mercapto acid derivatives 28 may be used.
These mercapto acid derivatives 28 are prepared from monosubstituted malonates 23 obtained either from commercial halides, or from halides 18, or from activated alcohols 22 (mesylate, tosylate and the like).
Schemes 5 and 6 describe the preparation of noncommercial halides 18 and activated alcohols 22. 
Compounds 18 may be obtained by two routes: by treatment in 9 N sodium hydroxide under reflux in the presence of THF or by using powdered K2CO3 in DMF at room temperature.
For the synthesis of the activated alcohols 22 of formula R2xe2x80x94CH(OZ)xe2x80x94(CH2)n2xe2x80x94Yxe2x80x94Ar (Z=Ms, Ts) in which R2, n2, Y and Ar have the definitions cited above in formula (I), the following method is used: 
Scheme 7 describes the synthesis of the monosubstituted malonates 23 obtained by reacting a commercial halide, a halide 18 or an activated alcohol 22 with diethyl malonate. 
The malonates 23 are obtained either from commercial halides, or from the halides 18 by reacting a diethyl malonate in the presence of sodium ethoxide in ethanol under reflux or from the activated alcohols 22 by reacting diethyl malonate in the presence of cesium fluoride in DMF at 60xc2x0 C.
The malonates 23 are converted to mercapto acid derivatives 28 according to scheme 8. 
The acrylic acids 25 are obtained by two routes:
a two-stage route via the diacids 24 obtained by saponification in 6 N sodium hydroxide under reflux, and then a Mannich reaction in the presence of paraformaldehyde, diethylamine in ethyl acetate under reflux;
a three-stage route via a monoacid 26 obtained by monosaponification in ethanolic potassium hydroxide at 0xc2x0 C. followed by a Mannich reaction giving the acrylic esters 27 and then a saponification with 2 N sodium hydroxide in an acetone-water mixture.
The derivatives 28 are obtained by Michael addition of thioacetic acid to the acrylic acids 25 at 70xc2x0 C.
The derivatives 28 are converted to mercaptoamine derivatives 30 according to scheme 9. 
The aminothiols of formula 30 are obtained according to two routes:
a two-stage route which consists in carrying out a Curtius reaction on the acids 28 using DPPA, NEt3 in toluene and an alcohol such as ethanol or benzyl alcohol at 80xc2x0 C. overnight. The carbonates 29 are then deprotected with a 10 N solution of sodium hydroxide in the presence of ethanol, under reflux for 2 hours under an inert atmosphere. After acidification with 3 N HCl, the aminothiols 30 are obtained;
a three-stage route where the Curtius reaction is carried out in tBuOH under reflux to give tert-butyl carbamate 31. The thioester functional group is then saponified with an aqueous solution of sodium hydroxide in the presence of MeOH to give the derivatives 32. The tert-butoxycarbonyl group is then deprotected with a solution of gaseous HCl in MeOH at xe2x88x9210xc2x0 C. The aminothiols 30 are thus obtained. 
The carbamates 31 are subjected to the action of N sodium hydroxide in ethanol and then to the action of a 0.3 M solution of iodine in ethanol to give the N-protected disulphides 33. The tert-butoxycarbonyl group is then deprotected with a gaseous HCl solution in MeOH at xe2x88x9210xc2x0 C. and the disulphides 34 are thus obtained. 
The benzyloxycarbonyl group is deprotected with a 30% gaseous HBr solution in acetic acid at room temperature to give the derivatives 35.
The inventors have also shown that the compounds (I) according to the invention have LTA4 hydrolase inhibiting properties.
They possess an advantageous therapeutic activity, in particular in the field of anti-inflammatory treatments.
They also possess an advantageous antiarthritic activity.
The compounds of the invention also have antipsoriatic properties.
Moreover, the inventors have shown that the compounds of the invention prevent the increase in the tissue levels of LTB4 which is induced by cyclooxygenase inhibitors.
They are thus useful for the prevention of certain paradoxical pro-inflammatory side effects of cyclooxygenase inhibitors.
Finally, LTB4 being the endogenous ligand for the receptor inducing proliferation of the peroxisomes, the compounds of the invention also find application in the fields of hepatoprotection and antimitotic action.
The subject of the present invention is thus also the use of the compounds of formula (I) as medicaments which act as inhibitors of the activity of LTA4 hydrolase, in particular for an anti-inflammatory or antiarthritic treatment.
Its subject is also the use of the compounds of the invention as antipsoriatic medicaments.
Its subject is also their use as hepatoprotective or antimitotic medicaments.
Its subject is also the use of such compounds as medicaments intended for the treatment of an overproduction of LTB4, induced in particular by cyclooxygenase inhibitors.
Its subject is also the use of such compounds (I) for the preparation of medicaments intended for inhibiting the activity of LTA4 hydrolase.
Its subject is in particular their use for the preparation of medicaments intended for the abovementioned treatments.
The compounds of formula (I) may be administered in a physiologically acceptable vehicle or excipient.
Accordingly, the subject of the present invention is also pharmaceutical compositions comprising a therapeutically effective quantity of at least one compound of formula (I) in combination with a physiologically acceptable vehicle or excipient.
The compounds (I) of the invention may also be used in combination with cyclooxygenase inhibitors.
The invention thus relates to medicaments or pharmaceutical compositions containing a therapeutically effective quantity of a compound (I) and a therapeutically effective quantity of a cyclooxygenase inhibiting compound, optionally in combination with a physiologically acceptable vehicle or excipient.
Examples of cyclooxygenase inhibitors useful according to the invention are aspirin (acetylsalicylic acid), ibuprofen and dichlofenac.
The medicaments or pharmaceutical compositions according to the invention may be advantageously administered by the local cutaneous or ocular routes, by the parenteral route or by the oral route, the latter being preferred.
The subject of the invention is also a method of treatment for inhibiting the activity of LTA4 hydrolase in humans.
Its subject is also such a method for the treatments indicated above.
Its subject is also a method of treating an overproduction of LTB4, in particular induced by cyclooxygenase inhibitors.